International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
Bipolar Disorders
January 13, 2023
Giovanni Martinotti, Bernardo Dell’osso, Giorgio Di Lorenzo et al.
72 citations
Esketamine nasal spray reduced depressive symptoms in people with treatment-resistant bipolar depression as effectively as in those with unipolar treatment-resistant depression, with no significant differences in response or remission rates after one and three months. The treatment also showed greater anxiety-reducing effects in the bipolar group. No treatment-emergent affective switch occurred, supporting the safety and tolerability of esketamine for bipolar treatment-resistant depression.
Psychiatry Research
July 29, 2023
Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al.
56 citations
Machine learning models predicted which patients with treatment-resistant depression would respond to esketamine nasal spray. In a retrospective study of 149 patients, three random forest classifiers achieved 68.53% accuracy for response at one month and 66.26% at three months, and 68.60% accuracy for remission at three months. Features such as severe anhedonia, anxious distress, mixed symptoms, and bipolarity positively predicted response and remission, while benzodiazepine use and depression severity were linked to delayed responses. The findings suggest machine learning may aid personalized treatment decisions for treatment-resistant depression.
European Neuropsychopharmacology
May 4, 2023
Stefania Chiappini, Giacomo D’andrea, Sergio De Filippis et al.
48 citations
Esketamine nasal spray reduces depression symptoms in patients with treatment-resistant depression who also have a substance use disorder. In 26 patients followed for three months, Montgomery-Asberg depression rating scale scores decreased significantly from baseline to one month and from one to three months. Side effects occurred in 73% of patients, most commonly dissociative symptoms and sedation, but none led to lasting harm and no abuse or misuse of the medication was reported. The findings suggest esketamine is effective and safe in this population, though the study is limited by its small sample and short follow-up.
Journal of Psychoactive Drugs
February 9, 2019
Lorenzo Moccia, A. Tofani, Marianna Mazza et al.
10 citations
A 23-year-old man developed a substance-induced psychotic disorder after intravenously injecting an unspecified amount of methoxetamine (MXE), a ketamine derivative hallucinogen. Clinically, he showed blunted affect, diminished social drive, loss of sense of purpose, and detachment from the environment. Psychometric tests revealed severe dissociation, lack of motivation, and mild impairments in verbal fluency, working memory, and attention. Brain scans using 18F-FDG PET/CT showed significantly reduced tracer uptake in the dorsolateral prefrontal cortex (DLPFC), a region critical for goal-oriented cognition, working memory, and attention. This case indicates that a single acute MXE intoxication can cause severe brain impairment.